The French soprano, Natalie Dessay (born Nathalie Dessaix), dropped the "h" in her first name in honor of Natalie Wood when she was in grade school and subsequently simplified the spelling of her surname. In her youth, Dessay had intended to be a ballet dancer, and then an actress. She discovered her talent for singing whilst taking acting classes, and shifted her artistic focus to music. Dessay was encouraged to study voice at the Conservatoire national de région de Bordeaux and gained experience as a chorister in Toulouse. At the competition Les Voix Nouvelles, run by France Telecom, she was awarded First Prize (Premier Prix de Concours) followed by a year's study at Paris Opera's Ecole d'Art Lyrique, where she sang Elisa in Mozart's Il re pastore. Also, she entered the International Mozart Competition at the Vienna Staatsoper, winning First Prize. Dessay is a lyric coloratura soprano.

Natalie Dessay was quickly approached by a number of theatres, and subsequently sang Blondchen, Madame Herz (in Der Schauspieldirektor), Zerbinetta and Zaïde at the Opéra National de Lyon and the Opera Bastille, as well as Adele in Die Fledermaus in Geneva. In April and May 1992 at the Opéra Bastille, she sang the role of Olympia in The Tales of Hoffmann with José van Dam. The Roman Polanski production was not well received, but it began the road to stardom for Dessay. Although she was soon featured in another production of Hoffmann, it would be over ten years before her return to Paris Opera in the same role. Soon after her Hoffmann run, Dessay joined the Vienna State Opera as Blondchen in The Abduction From The Seraglio by W.A. Mozart. She was then asked to replace Cheryl Studer in all three female roles in a German production of Hoffmann. In December 1993, Dessay's Olympia received acclaim from the Vienna audiences and praise from Plácido Domingo.

Natalie Dessay's next project was to have been Sophie von Faninal alongside Barbara Bonney in Richard Strauss' Der Rosenkavalier under Carlos Kleiber. However, he died before the project came to fruition. Blondchen in Die Entführung and Zerbinetta in Ariadne auf Naxos became her best-known and most often played roles. In October 1994 Dessay made her Metropolitan Opera debut in New York in the role of Fiakermilli in Strauss' Arabella, and returned there in September 1997 as Zerbinetta and February 1998 as Olympia. The Staatsoper approached Dessay with two operas: Richard Strauss' Die schweigsame Frau and an unfinished opera by Alban Berg, Lulu. Dessay declined the latter. At the festival of Aix-en-Provence, Dessay first performed the role of Queen of the Night in Mozart's The Magic Flute. Although she was hesitant to perform the role, saying that she didn't want to play any "evil" characters, director Robert Carsen convinced her that this Queen would be different, almost a sister to Pamina. Dessay agreed to do the role, claiming it would be a one-time series of performances. There followed a years-long series of "final" performances of the Queen of the Night.

During the 2001-2002 season in Vienna, Natalie Dessay began to experience vocal difficulties and had to be replaced in almost all of the performances of La Sonnambula. Subsequently, she was forced to cancel several other performances, including a French version of Lucia in Lyon and a Zerbinetta at the Royal Opera House in London. She withdrew from the stage and underwent surgery on one of her vocal cords in July 2002. In February 2003, she returned to live performances in a Paris concert. In March 2003, she sang the role of Zerbinetta at the Metropolitan Opera, a performance which has been filmed.

In the summer of 2003, Natalie Dessay gave a concert at the Santa Fe Opera. She was so attracted to New Mexico in general (and to Santa Fe, New Mexico in particular) that, when she was invited to return the following season, general director Richard Gaddes re-arranged the 2004 summer festival program and presented La Sonnambula instead of an already-scheduled opera. Her most recent performances over the summer 2006 season in Santa Fe have been in the role of Pamina in The Magic Flute. Dessay was the singing voice of opera singer Anna Sörensen in the movie Joyeux Noël (2005).

Another setback caused additional cancellations and further surgery, but by mid-2005 she was back on stage. However, this has resulted in some re-thinking of her roles, abandoning some and taking up new ones. These include Massenet's Manon, "Juliette" in Charles Gounod's Roméo et Juliette at the Met, Donizetti's Lucia, and a first Violetta in La Traviata.

The 2006-2007 season schedule included Lucia di Lammermoor and La sonnambula in Paris, La fille du régiment in London and Vienna, plus a Laurent Pelly directed La fille du regiment at the Royal Opera House in London and a Manon in Barcelona. She opened the 2007-2008 season at the Met as Lucia and is also scheduled to repeat the La fille du regiment that season. San Francisco Opera has announced that Dessay is scheduled to sing the role of Lucia in Lucia di Lammermoor in June 2008. She is also scheduled to sing Violetta in La Traviata at Santa Fe Opera in 2009.